Effect of in vivo antiestrogen pretreatment on rabbit atrial chronotropic response to histamine

The chronotropic response (delta rate) to histamine (1.4 to 18 X 10(-6) M) of isolated atria from antiestrogen (tamoxifen)-pretreated immature female rabbit was investigated. Tamoxifen treatment (1.0 and 10.0 mg/kg/day for 14 days) had no significant effect on the delta rate. The Rmax and D1/2max were not significantly different in the two tamoxifen-treated groups compared to the oil-treated (1.0 ml/kg/day for 14 days) control group. Cimetidine (2.8 X 10(-7) M) inhibited the delta rate to histamine in all groups: control, 27%; tamoxifen (1.0 mg/kg), 38%; and tamoxifen (10.0 mg/kg), 28%. Only the low dose of tamoxifen was found to be estrogenic (uterotropic). We conclude that tamoxifen pretreatment, both at estrogen-agonist and estrogen-antagonist doses, is without effect on atrial chronotropic response to histamine.